TAG-72-Binding CAR Polypeptides for Targeted Immune Activation
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Solution Overview
Problem
Current cancer treatments, including surgery, radiation therapy, and chemotherapy, have limitations in effectively harnessing the immune system for targeted cancer therapy, particularly in addressing TAG-72-expressing cancers.
Innovation Solution
Development of chimeric antigen receptor (CAR) polypeptides that incorporate an anti-TAG-72 binding agent, such as antibody fragments or aptamers, to specifically target and kill TAG-72-expressing cancer cells, combined with immune effector cells like T cells or NK cells genetically modified to express these CARs, facilitating adoptive cell transfer for immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional cancer treatments (surgery, radiation therapy, chemotherapy) are used, then cancer can be treated with established methods, but the immune system cannot be effectively harnessed for targeted therapy
Solution Approach 1:
The patent uses chimeric antigen receptors (CARs) as intermediary structures that bridge the immune system and cancer cells. The CAR comprises an ectodomain with anti-TAG-72 binding agent that recognizes cancer cells, a transmembrane domain for cellular anchoring, and an endodomain with signaling and co-stimulatory regions that activate immune effector cells. This intermediary structure enables the immune system to specifically target and eliminate TAG-72-expressing cancers while maintaining treatment reliability.
2Adaptability or versatility
If the immune system is utilized for cancer therapy, then targeted therapy potential is unlocked, but current approaches lack effective mechanisms to activate immune cells against specific cancer targets
Solution Approach 1:
The patent merges multiple functional domains into a single chimeric antigen receptor molecule. The CAR combines the antigen recognition function (ectodomain with anti-TAG-72 binding agent), membrane anchoring function (transmembrane domain), and immune activation function (endodomain with signaling and co-stimulatory regions). This merged structure simplifies the implementation of targeted immunotherapy by providing all necessary functions in one engineered receptor, making the therapy easier to operate and implement.
3Reliability
If CAR polypeptides with incomplete endodomains are used, then safety control is improved through dual binding requirements, but the complexity of immune cell activation increases
Solution Approach 1:
The patent implements preliminary anti-action by designing CAR polypeptides with incomplete endodomains that prevent premature or unintended immune cell activation. The CAR requires simultaneous binding to TAG-72 on cancer cells and interaction with a second CAR or endogenous T-cell receptor to complete the activation signal. This preliminary safety check ensures that immune cells are only activated when proper target recognition occurs, preventing off-target effects while the dual-binding mechanism provides inherent safety control.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The CAR polypeptides enable targeted anti-tumor immunity by specifically binding to TAG-72-expressing cancer cells, activating immune effector cells to kill cancer cells, thereby providing an effective immunotherapy approach for TAG-72-expressing cancers.
Implementation Method 1
The disclosed CAR polypeptides contain in an ectodomain an anti-TAG-72 binding agent that can bind TAG-72-expressing cancer cells. The anti-TAG-72 binding agent is in some embodiments an antibody fragment that specifically binds TAG-72.
Implementation Method 2
the endodomain can contain a signaling domain and one or more co-stimulatory signaling regions... the immune effector cell is activated unless it and a second CAR polypeptide (or endogenous T-cell receptor) that contains the missing domain both bind their respective antigens
Data Source
AI summary
Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill TAG-72-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a TAG-72-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.